Nod2-Dependent Regulation of Innate and Adaptive Immunity in the Intestinal Tract

TLDR

Nod2 mutations are common in Crohn’s disease, yet its intestinal role remains poorly understood. Nod2-deficient mice lack muramyl dipeptide–mediated protection, are vulnerable to oral bacterial infection, and fail to express cryptdins, underscoring Nod2’s essential role in intestinal bacterial immunity.

Abstract

The gene encoding the Nod2 protein is frequently mutated in Crohn's disease (CD) patients, although the physiological function of Nod2 in the intestine remains elusive. Here we show that protective immunity mediated by Nod2 recognition of bacterial muramyl dipeptide is abolished in Nod2-deficient mice. These animals are susceptible to bacterial infection via the oral route but not through intravenous or peritoneal delivery. Nod2 is required for the expression of a subgroup of intestinal anti-microbial peptides, known as cryptdins. The Nod2 protein is thus a critical regulator of bacterial immunity within the intestine, providing a possible mechanism for Nod2 mutations in CD.